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Is More CBD Better? The Science Behind CBD Dosing for Anxiety and Other Conditions

December 14, 2017
Is More CBD Better? The Science Behind CBD Dosing for Anxiety and Other Conditions(cosmin4000/iStock)

In 2015, the National Institute of Health allotted $21.2 million of its $111 million cannabinoid research budget towards projects exploring the medicinal potential of these compounds. These projects proposed to manipulate the body’s endocannabinoid system, either by modifying endocannabinoids or with phytocannabinoids from the cannabis plant.

While the primary psychoactive phytocannabinoid, delta 9-THC, has acknowledged medicinal value, cannabidiol (CBD) is widely known for its broad range of potential medicinal uses. In recognition of CBD’s vast potential, over $9 million in grants were awarded in 2015 to fund CBD-specific medicinal research.

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Much of this research has centered around the treatment of epilepsy, with studies showing that CBD has significant potential for treating the condition in children at high doses. A daily dose over 600 mg reduced seizure frequency by 39%. While this is a far greater amount than you’d find in many of the CBD consumables available at your local dispensary, many retail CBD products with lower levels of the cannabinoid are reported to be effective at treating anxiety, pain, and a host of other disorders, either through self-experimentation or anecdotal reports.

So why not crank up the CBD dose to reduce your anxiety? If a little is good, shouldn’t a lot be better? It turns out that for CBD, the answer is no; CBD’s medicinal efficacy might require a particular dose range. Call it a “Goldilocks Zone,” where there’s not too much CBD but not too little, either.

Intriguingly, this Goldilocks Zone differs for each disorder. For instance, CBD appears to treat anxiety at relatively low doses compared to the high doses used to treat epilepsy.

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Overshooting the Goldilocks Zone when trying to treat a given condition may reduce the efficacy of CBD. An animal study published back in 1990 found that low to moderate CBD doses reduced anxiety, but CBD’s anti-anxiety effect disappeared at higher doses. Importantly, the authors note an inverted-U response to CBD. Out of the four doses tested, the lowest dose had a moderate anti-anxiety effect, the second-lowest dose had the greatest anti-anxiety effect, the third dose had a moderate effect, and the highest dose had no effect.

While it may sound out of the ordinary, this “inverted-U” effect is actually quite common among drugs that affect multiple brain receptors, as CBD does. In fact, 37% of published toxicology articles report some degree of an inverted-U response, indicating that this is not a random event but instead reflects differential drug effects on brain targets.

Different doses of CBD may actually be more beneficial, depending on the ailment or condition being treated. (Leafly)

The wide spectrum of CBD’s medical indications—it is used as a treatment for pain, anxiety, post-traumatic stress disorder, and other conditions—reflects its diverse set of brain and body targets. Since each of these many medical problems is impacted by CBD acting on specific receptors in the brain and body, differences in sensitivity for these targets may underlie CBD’s inverted U-response and define its Goldilocks Zone.

Right: The brain contains a huge a number of brain cells (neurons). Each neuron, represented here as a hexagon, is connected to many others. Left: The synapse is the site where two neurons communicate with each other. The “sender neuron” releases chemical signals called neurotransmitters, which stimulate receptors on the “receiver neuron.” There are many different receptor types in the brain, each one sensitive to different neurotransmitters. (Leafly)

Renowned cannabinoid pharmacologist Roger Pertwee described CBD actions at low, medium, and high doses in an oft-cited review published in The British Journal of Pharmacology. As expected, low doses of CBD impact fewer neural targets than high doses. At relatively low doses, CBD can block endocannabinoids like anandamide and phytocannabinoids like delta 9-THC from interacting with receptors in the nervous system. This blocking action is thought to explain CBD’s ability to reduce the adverse effects that can accompany delta 9-THC exposure such as anxiety.

Left: THC directly stimulates the CB1 receptor. This interaction underlies the major psychoactive effects of Cannabis consumption. Right: CBD reduces, or “antagonizes,” THC’s ability to stimulate CB1 receptors. This can decrease some of THC’s effects, especially negative effects like anxiety and short-term memory impairment. (Leafly)

CBD’s anti-anxiety effects can also be attributed to its activation and enhancement of specific serotonin receptors. Serotonin is an important neurotransmitter involved in mood regulation and stress response; low serotonin levels are thought to contribute to conditions including generalized anxiety disorder and major depression. A common pharmacological treatment for these conditions involves enhancing the amount of serotonin available in an effort to activate the receptors using selective serotonin reuptake inhibitors, or SSRIs.

Rodent studies of CBD in anxiety and stress reveal that CBD similarly enhances serotonin receptor activation. In rats, a low-to-moderate dose of CBD has anti-anxiety effects following a stressful period of restraint (the rat equivalent of being placed in a straitjacket for an hour), but these anti-anxiety effects go away when the serotonin receptor 5-HT1a is blocked ahead of time. This suggests that low doses of CBD near the peak of the rodent’s inverted-U response reduce anxiety by activating 5-HT1a receptors.

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Similar CBD doses in humans have been shown to be effective at reducing anxiety in individuals with generalized social anxiety disorder, and low to moderate doses are effective at reducing stress and improving performance in a simulated public speaking event. These positive effects are associated with a restoration of normal brain activity in key regions associated with anxiety and emotional dysregulation.

The positive effects of CBD in treating anxiety are experienced at about 25% of the dose used to treat epilepsy. That higher effective dose level reflects additional CBD brain targets beyond those active in treating anxiety.

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While CBD activation of 5-HT1a receptors is insufficient to protect against seizures, a promising target for CBD’s antiepileptic effects is the receptor GPR55, which initiates a cascade of events that can have diverse effects in brain cells. CBD is an antagonist of GPR55, blocking its function and altering brain activity in a way that may protect against seizures. When administered in higher doses, though, the benefits of lower concentrations may be lost. Anti-anxiety effects, for instance, seem to be obstructed while higher concentrations of CBD work to block GPR55 receptors.

Identifying CBD’s many neural targets and their sensitivity is an exciting area of ongoing research. But knowing the optimal CBD dose for treating different conditions is a critical component of successful CBD treatment. The current research suggests that anxiety and depression-related disorders (e.g., obsessive compulsive disorder, autism, acute stress) respond best to low-moderate CBD doses, while epilepsy responds best to higher CBD doses.

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Being able to titrate CBD dosing for specific disorders will lead to more efficacious CBD-centric therapies and reveal treatment strategies that may be able to combat multiple ailments at once. CBD’s Goldilocks Zone for treating anxiety illustrates the need for an improved understanding of the compound’s therapeutic mechanisms, while highlighting its vast treatment potential.

Josh Kaplan's Bio Image

Josh Kaplan

Josh Kaplan, Ph.D., is an Assistant Professor of Behavioral Neuroscience at Western Washington University. He is a passionate science writer, educator, and runs a laboratory that researches cannabis' developmental and therapeutic effects.

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  • 2Bdtrmnd

    “The positive effects of CBD in treating anxiety are experienced at about 25% of the dose used to treat epilepsy.”

    150 mg a day ($225 a month at the low end) is still too costly for the average person suffering with chronic pain and anxiety. When is this stuff going to become affordable, and why the hell can’t I find high cbd hemp seeds to grow my own?

    • Kim Dunshie Herning

      Depending upon where you live (legal in your state) you can find high CBD strains to grow on your own. Research strains that are high in CBD like Bird, Taint, Cindy OG. Many of these strains of cannabis are CBD dominate with two or three times the amount of CBD vs. THC. Many studies have shown by adding a small amount of THC to CBD help the medicine work better. It is most cost effective to grow outside, but the minute you start growing inside you are paying for electricity. And depending on your electricity costs it may cost you close to the same amount of money to grow as it would to buy commercially prepared CBD oil. I had to do the break down here as we have been buying Charlotte’s Web Everyday Advanced that is $247.00 for 100ML. Which will last almost two months for three doses a day. For us, although legal to grow, we determined it is more cost effective to purchase the oil because electricity is super expensive here. I watch for sales which usually brings the price down to $200.00 a bottle. The suggested dose is 50mg.

    • Bill

      You can find them….Charlotte’s Web is one that comes to mind. Quite honestly though the only real affordable way to treat with cannabis is to grow it and process your own medicine, and even more economical still is to not process it, but rather to just vaporize it and inhale it.

    • I agree. That’s why a program where you can get your product free is preferable.

    • Lauren

      I use closer to 10 mg a day for anxiety and have had amazing results.

    • nobody

      If you’re disabled or low income or a vet, check out lazarus.

  • zenshade@protonmail.com

    It is commonly known that when seperating the cannabinoids into single purified extracts, like pure CBD, a bell shaped response to the efficancy of the constituant is observed. This Is the old pharmaceutical way of trying to isolate specific compunds for “marketing and patent making” these compunds are not safe for human consumption and will eventually lead to degraded health in people and patients. However this Bellshaped response does not occur when the whole cannabis extract is used.

    http://cannabisclinicians.org/wp-content/uploads/2015/03/CBD-vrs-whole-plant-CBD-2015.pdf

  • Janet Busvek

    I live in TN which prohibits Cannabis. I want to know if anyone knows whether CBD extracts will help chronic pain. I am totally confused about type and dosing because it is very expensive. So before buying I would appreciate some direction by anyone who can help. Thank you, Janet

    • Celeste Yarnall

      After 3 years of research for my own health crisis with cancer and chemo, I finally found a product that I am passionate about and now love to pay forward and that is because of the scientist who developed it, his name is Dr. Christopher Shade Ph.D and he created the liposomal sublingual system with a nano emulsification but all we need to know is it really works. 2 pumps right from the bottle under your tongue and your will have absorption immediately and feel balanced right way. Check it out at http://www.artofwellness.primemybody.com

    • Denise Lawrence-Kenney

      CBDISTILLERY is a great place to start and a little more affordable it’s also very informative and reviews from the customers is fabulous again, very informative. Good luck dear.

    • Open Minds

      Hi Janet, what is the cause of the chronic pain? Depending on the cause, THC or CBD, or a combination of both might be your best option. Also, don’t buy products from people that promote their products in the comments section. Here is a link to all the studies done on pain and cannabis: http://www.thctotalhealthcare.com/category/pain-2/

    • bluehawk2

      I am licensed by the state of Tennessee, in accordance with the Federal Farm Bill of 2014, to grow and process Industrial Hemp in the State of Tennessee, Industrial Hemp is defined as Cannabis containing less than .3% delta 9 THC. Strains of industrial hemp may have from 2 to 14% CBD. We use a multi solvent extraction process and produce a black extract what I believe is the broadest spectrum extract available, complete with , terpenes, CBDA, CBDB. terpenes, and about 2 mg of Tdelta HCs per gram. our extract contains a little bit of everything, but apparently not enough to reach receptor saturation for any one compound. The Israelis found a Full Spectrum olive oil extract had a linear dose response curve, (effects go up with dose) over a broad range, where as CBD isolates, (individual distillation cuts from the full spectrum that come off at a given temperature and pressure) have a bullet shaped dose response curve.

      • bryndon golya

        I sell full spectrum cbd products and work directly with the farm. All our products are Co2 extracted. Are you saying you believe isolates have a similar response to the full spectrum products in respect to the bell curve? Literally all the info I can find says otherwise but I’m always open to learn if this is the contrary.

  • Autumn

    This was a really fascinating read! Thank you for breaking it down for us. I still can’t believe how expensive this is despite being proven how it can help so many different ailments. I hope we can work out some better funding for this. Hopefully more articles like this will help pave the way! We’re discussing this here: https://www.greenapple.md/forums/stress-anxiety/science-behind-cbd-anxiety/

  • Paul

    I have been unsuccessfully researching what dose of CBD works for arthritis and back pain and insomina. Does anyone have any idea what dose works best for my symptoms? thanx.

  • Susanna Withers

    This article is great in that now I know I need a “low-to-moderate” dose of CBD…. but it’s missing one crucial aspect: numbers. How many mg’s a day is “low-to-moderate”? The only number I have to reference from this article is that 600mg a day is a “far greater amount” than I’d usually find in products. So… does that mean that 600 is the high point, 300mg/day is in the middle of the spectrum, and 50mg a day is super low? Or does that mean that 600mg is way out there, 300 is high, 150 moderate and 10 super low? Please, give us some numbers. When it comes to actually knowing what to do, this article is pretty worthless.

  • Andrew Jackson

    Have you ever felt sick to your stomach after taking CBD oil?